Scott M Schuetze1, J Kyle Wathen2, David R Lucas3, Edwin Choy4, Brian L Samuels5, Arthur P Staddon6, Kristen N Ganjoo7, Margaret von Mehren8, Warren A Chow9, David M Loeb10, Hussein A Tawbi11, Daniel A Rushing12, Shreyaskumar R Patel13, Dafydd G Thomas14, Rashmi Chugh1, Denise K Reinke15, Laurence H Baker1. 1. Division of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan. 2. Department of Biostatistics, Johnson & Johnson, New Brunswick, New Jersey. 3. Anatomic Pathology, University of Michigan, Ann Arbor, Michigan. 4. Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 5. Northwest Oncology, Post Falls, Idaho. 6. Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 7. Medical Oncology, Stanford Medical Institute, Stanford, California. 8. Division of Medical Oncology and Hematology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 9. Department of Medical Oncology and Therapeutics Research, City of Hope Medical Center, Duarte, California. 10. Division of Pediatric Oncology, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland. 11. Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. 12. Divison of Hematology/Oncology, Department of Medicine, Indiana University, Indianapolis, Indiana. 13. Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 14. Molecular Pathology, University of Michigan, Ann Arbor, Michigan. 15. Sarcoma Alliance for Research through Collaboration, Ann Arbor, Michigan.
Abstract
BACKGROUND: Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. METHODS: Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%. RESULTS: A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients. CONCLUSIONS: Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity.
BACKGROUND:Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advanced sarcoma. METHODS:Patients received dasatinib twice daily. The primary objective was to estimate the clinical benefit rate (CBR) (complete response or partial response within 6 months or stable disease duration of ≥6 months) with a target of ≥25%. Patients were enrolled into 1 of 7 different cohorts and assessed by imaging every 8 weeks using Choi criteria tumor response and a Bayesian hierarchical design. For each subtype, enrollment was stopped after a minimum of 9 patients were treated if there was a <1% chance the CBR was ≥25%. RESULTS: A total of 200 patients were enrolled. Accrual was stopped early in 5 cohorts because of low CBR. The leiomyosarcoma (LMS) and undifferentiated pleomorphic sarcoma (UPS) cohorts fully accrued and 6 of 47 and 8 of 42 evaluable patients, respectively, exhibited clinical benefit. The probability that the CBR was ≥25% in the LMS and UPS cohorts was 0.008 and 0.10, respectively. The median progression-free survival ranged from 0.9 months in patients with rhabdomyosarcoma to 2.2 months in patients with LMS. The median overall survival was 8.6 months. The most frequent adverse events were constitutional, gastrointestinal, and respiratory, and 36% of patients required dose reduction for toxicity. Serious adverse events attributed to therapy occurred in 11% of patients. CONCLUSIONS:Dasatinib may have activity in patients with UPS but is inactive as a single agent in the other sarcoma subtypes included herein. The Bayesian design allowed for the early termination of accrual in 5 subtypes because of lack of drug activity.
Authors: Sandra P D'Angelo; Alexander N Shoushtari; Mary Louise Keohan; Mark A Dickson; Mrinal M Gounder; Ping Chi; Jennifer K Loo; Leigh Gaffney; Lee Schneider; Zarine Patel; Joseph Patrick Erinjeri; Mark J Bluth; Ana Sjoberg; Howard Streicher; Naoko Takebe; Li-Xuan Qin; Cristina Antonescu; Ronald P DeMatteo; Richard D Carvajal; William D Tap Journal: Clin Cancer Res Date: 2016-12-22 Impact factor: 12.531
Authors: Josephine H Haduong; Christine M Heske; Wendy Allen-Rhoades; Wei Xue; Lisa A Teot; David A Rodeberg; Sarah S Donaldson; Aaron Weiss; Douglas S Hawkins; Rajkumar Venkatramani Journal: Pediatr Blood Cancer Date: 2022-02-07 Impact factor: 3.167
Authors: Scott M Schuetze; Vanessa Bolejack; Dafydd G Thomas; Margaret von Mehren; Shreyaskumar Patel; Brian Samuels; Edwin Choy; Gina D'Amato; Arthur P Staddon; Kristen N Ganjoo; Warren A Chow; Daniel A Rushing; Charles A Forscher; Dennis A Priebat; David M Loeb; Rashmi Chugh; Scott Okuno; Denise K Reinke; Laurence H Baker Journal: JAMA Oncol Date: 2018-06-01 Impact factor: 31.777